Vemurafenib, propane-1-sulfonic acid {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]-2,4-difluoro-phenyl}-amide, has the following chemical structure:

Vemurafenib is a BRAF kinase inhibitor, which is marketed under the trade name ZELBORAF® for the treatment of patients with metastatic melanoma with the BRAF V600E mutation. Vemurafenib tablets contains 240 mg of vemurafenib as a co-precipitate of vemurafenib and hypromellose acetate succinate (HPMCAS).
U.S. Pat. No. 7,863,288 discloses Vemurafenib. WO 2010/114928 discloses crystalline forms I and II of Vemurafenib; its mesylate, tosylate, maleate, oxalate, dichloroacetate salts, as well as solid dispersions that include Vemurafenib and a ionic polymer, in a ratio of Vemurafenib and the ionic polymer of about 1:9 to about 5:5, preferably about 3:7 (by weight). WO 2010/129570 discloses non-crystalline complexes of Vemurafenib and its L-arginine and L-lysine salts. WO 2011/057974 describes a solid dispersion of Vemurafenib, and describes that the amorphous form of Vemurafenib has improved solubility in water as compared to the crystalline form, but it is unstable. WO 2012/161776 discloses additional solid forms and salts of Vemurafenib, including a hydrochloride salt.
Different salts and solid state forms (including solvated forms) of an active pharmaceutical ingredient may possess different properties. Such variations in the properties of different salts and solid state forms and solvates may provide a basis for improving formulation, for example, by facilitating better processing or handling characteristics, improving the dissolution profile, or improving stability (polymorph as well as chemical stability) and shelf-life. These variations in the properties of different salts and solid state forms may also provide improvements to the final dosage form, for instance, if they serve to improve bioavailability. Different salts and solid state forms and solvates of an active pharmaceutical ingredient may also give rise to a variety of polymorphs or crystalline forms, which may in turn provide additional opportunities to use variations in the properties and characteristics of a solid active pharmaceutical ingredient for providing an improved product.
Polymorphism, the occurrence of different crystal forms, is a property of some molecules and molecular complexes. A single compound, like Vemurafenib, may give rise to a variety of polymorphs having distinct crystal structures and physical properties like melting point, thermal behaviors (e.g. measured by thermogravimetric analysis—“TGA”, or differential scanning calorimetry—“DSC”), powder X-ray diffraction (PXRD) pattern, infrared absorption fingerprint, Raman absorption fingerprint, and solid state (13C—)NMR spectrum. One or more of these techniques may be used to distinguish different polymorphic forms of a compound.
Discovering new salts and polymorphic forms and solvates of a pharmaceutical product can provide materials having desirable processing properties, such as ease of handling, ease of processing, storage stability, and ease of purification or as desirable intermediate crystal forms that facilitate conversion to other salts or polymorphic forms. New salts, polymorphic forms and solvates of a pharmaceutically useful compound can also provide an opportunity to improve the performance characteristics of a pharmaceutical product (dissolution profile, bioavailability, etc.). It enlarges the repertoire of materials that a formulation scientist has available for formulation optimization, for example by providing a product with different properties, e.g., a different crystal habit, higher crystallinity or polymorphic stability which may offer better processing or handling characteristics, improved dissolution profile, or improved shelf-life. For at least these reasons, there is a need for additional salts and solid state forms (including solvated forms) of vemurafenib.